Indeno[4,3a-b]furan, decahydro-2,2,7,7,8,9,9-heptamethyl-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 September 2003 to 07 October 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

449-360-4

EC Name:

-

Cas Number:

647828-16-8

Molecular formula:

C18H32O

IUPAC Name:

decahydro-2,2,6,6,7,8,8-heptamethyl-2H-Indeno[4,5-b] furan

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: At least 200g, the weight variation did not exceed ± 20% of the mean weight for each sex
- Fasting period before study: Not applicable
- Housing: Housed in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE:
- Area of exposure: 10 % of total body surface area
- Type of wrap if used: Surgical gauze, semi-occluded with a piece of self adhesive bandage

REMOVAL OF TEST SUBSTANCE:
- Washing: yes
- Time after start of exposure: 24 hours

TEST MATERIAL:
- Amount(s) applied: 2.15 mL/kg
- Constant volume or concentration used: yes, 2000 mg/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Body weights were recorded prior to dosing and on day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, gross pathology.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Confidence limits are not applicable in this limit test.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Other observations: There were no signs of dermal irritation.

Any other information on results incl. tables

Table 1. Individual Clinical Observations and Mortality Data.

Dose Level mg/kg bw	Animal Number and Sex	Effects Noted After Initiation of Exposure (Hours)				Effects Noted After Initiation of Exposure (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-4 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-4 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 2. Individual Dermal Reactions - Males.

Dose Level mg/kg bw	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1-1 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1-2 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1-3 Male	Erythema Oedema Other a	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1-4 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0

 
Table 3. Individual Dermal Reactions - Females.

Dose Level mg/kg bw	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2-1 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2-2 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2-3 Female	Erythema Oedema Other a	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2-4 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0

 

Table 4. Individual Body weights and Weekly Body weight Changes.

Dose Level mg/kg bw	Animal Number and Sex	Body weight (g) at Day			Body weight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Male	293	336	389	43	53
	1-1 Male	269	321	360	52	39
	1-2 Male	279	328	369	49	41
	1-3 Male	297	346	385	49	39
	1-4 Male	297	347	393	50	46
	2-0 Female	247	266	283	19	17
	2-1 Female	231	239	258	8	19
	2-2 Female	224	235	259	11	24
	2-3 Female	239	253	264	14	11
	2-4 Female	225	242	252	17	10

 

Table 5. Individual Necropsy Findings.

Dose Level mg/kg bw	Animal Number and Sex	Time of Death	Macroscpoic Observations
2000	1-0 Male	Killed Day 14	No abnormalities detected
	1-1 Male	Killed Day 14	No abnormalities detected
	1-2 Male	Killed Day 14	No abnormalities detected
	1-3 Male	Killed Day 14	No abnormalities detected
	1-4 Male	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Killed Day 14	No abnormalities detected
	2-4 Female	Killed Day 14	No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

other: Not acute harmful according to EU CLP (EC 1272/2008 and its amendments).

Conclusions:

The substance has an LD50 of > 2000 mg/kg bw in an OECD TG 402 test.

Executive summary:

To assess the acute dermal toxicity of the test substance, an acute dermal toxicity study was performed in accordance with OECD TG 402 and under GLP conditions. A group of ten Sprague-Dawley CD rats (five males and five females) was given a single, 24-hour, semi-occluded dermal application of undiluted test substance to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. No mortality was observed. There were no signs of systemic toxicity and no dermal irritation was observed. All animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD₅₀) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.